tbuckley/cabot-search huggingface dataset:
Surgical polarimetric endoscopy for the detection of laryngeal cancer
Authors: Ji Qi, Taranjit Tatla, Eranga Nissanka-Jayasuriya, Alan Yilun Yuan, Danail Stoyanov, Daniel S. Elson
Journal: Nature Biomedical Engineering (2023)

The standard-of-care for the detection of laryngeal pathologies involves distinguishing suspicious lesions from surrounding healthy tissue via contrasts in colour and texture captured by white-light endoscopy. However, the technique is insufficiently sensitive and thus leads to unsatisfactory rates of false negatives. Here we show that laryngeal lesions can be better detected in real time by taking advantage of differences in the light-polarization properties of cancer and healthy tissues. By measuring differences in polarized-light retardance and depolarization, the technique, which we named 'surgical polarimetric endoscopy' (SPE), generates about one-order-of-magnitude greater contrast than white-light endoscopy, and hence allows for the better discrimination of cancerous lesions, as we show with patients diagnosed with squamous cell carcinoma. Polarimetric imaging of excised and stained slices of laryngeal tissue indicated that changes in the retardance of polarized light can be largely attributed to architectural features of the tissue. We also assessed SPE to aid routine transoral laser surgery for the removal of a cancerous lesion, indicating that SPE can complement white-light endoscopy for the detection of laryngeal cancer.
Error in Figure
Authors: Barak Richman, Kevin Schulman
Journal: JAMA (2023)

Jason C. Yam, MPH; Xiu Juan Zhang, PhD; Yuzhou Zhang, PhD; Benjamin H. K. Yip, PhD; Fangyao Tang, PhD; Emily S. Wong, MBChB; Christine H. T. Bui, PhD; Ka Wai Kam, MSc; Mandy P. H. Ng, MHM; Simon T. Ko, MBBS; Wilson W.K. Yip, MBChB; Alvin L. Young, MMedSc; Clement C. Tham, BM, BCh; Li Jia Chen, PhD; Chi Pui Pang, DPhil
Best practices for single-cell analysis across modalities
Authors: Lukas Heumos, Anna C. Schaar, Christopher Lance, Anastasia Litinetskaya, Felix Drost, Luke Zappia, Malte D. Lücken, Daniel C. Strobl, Juan Henao, Fabiola Curion, Hananeh Aliee, Meshal Ansari, Pau Badia-i-Mompel, Maren Büttner, Emma Dann, Daniel Dimitrov, Leander Dony, Amit Frishberg, Dongze He, Soroor Hediyeh-zadeh, Leon Hetzel, Ignacio L. Ibarra, Matthew G. Jones, Mohammad Lotfollahi, Laura D. Martens, Christian L. Müller, Mor Nitzan, Johannes Ostner, Giovanni Palla, Rob Patro, Zoe Piran, Ciro Ramírez-Suástegui, Julio Saez-Rodriguez, Hirak Sarkar, Benjamin Schubert, Lisa Sikkema, Avi Srivastava, Jovan Tanevski, Isaac Virshup, Philipp Weiler, Herbert B. Schiller, Fabian J. Theis
Journal: Nature Reviews Genetics (2023)
Correction: TNFRSF19 Inhibits TGFβ Signaling through Interaction with TGFβ Receptor Type 1 to Promote Tumorigenesis
Authors: Chengcheng Deng, Yu-Xin Lin, Xue-Kang Qi, Gui-Ping He, Yuchen Zhang, Hao-Jiong Zhang, Miao Xu, Qi-Sheng Feng, Jin-Xin Bei, Yi-Xin Zeng, Lin Feng
Journal: Cancer Research (2023)

In the original version of this article (1), there was an error in Fig. 2E.Specifically, an image of primary tumor spheroid growth from WT HNE-1 cells was mistakenly used to represent secondary tumor growth in WT HNE-1 cells.The correct image has been provided, and the error has been corrected in the latest online HTML and PDF versions of this article.The authors regret this error.
Assessment of Electronic Nicotine Delivery Systems With Cigarette Use and Self-reported Wheezing in the US Adult Population
Authors: Luz M. Sánchez-Romero, Irina Bondarenko, Marie Knoll, Jana L. Hirschtick, Steven Cook, Nancy L. Fleischer, David T. Levy
Journal: JAMA Network Open (2023)

The prevalence of electronic nicotine delivery systems (ENDS) use has increased, leading to a concern about their respiratory health outcomes. It is unclear whether ENDS use increases the risk of wheezing, a common symptom of respiratory conditions.To provide an analysis of the longitudinal association between ENDS and cigarette use and self-reported wheezing among US adults.The US nationally representative Population Assessment of Tobacco and Health (PATH) Study was used. Longitudinal data for adults 18 years or older from wave 1 (2013-2014) to wave 5 (2018-2019) were analyzed. Data were analyzed from August 2021 to January 2023.The prevalence of self-reported wheezing (waves 2-5) was estimated for 6 strata of tobacco product use (never cigarette and noncurrent ENDS use, never cigarette and current ENDS use, current cigarette and noncurrent ENDS use, current cigarette and current ENDS use, former cigarette and noncurrent ENDS use, and former cigarette and current ENDS use). A generalized estimating equations framework evaluated the association between cigarette and ENDS use and self-reported wheezing at the subsequent wave. An interaction term between cigarette and ENDS use was added to estimate the association between joint cigarette and ENDS use categories and the association of ENDS within strata of cigarette use.The analytical sample consisted of 17 075 US adults with a mean (SD) age of 45.4 (17) years, of whom 8922 (51%) were female and 10 242 (66%) were Non-Hispanic White. When compared with never cigarette and noncurrent ENDS use, the greatest association in reporting wheezing was for current cigarette and current ENDS use (adjusted odds ratio [AOR], 3.26; 95% CI, 2.82-3.77), which was similar to current cigarette and noncurrent ENDS use (AOR, 3.20; 95% CI, 2.91-3.51) and substantially greater than former cigarette and current ENDS use (AOR, 1.94; 95% CI, 1.57-2.41). Associations were small and not statistically significant for the odds of self-reported wheezing among never cigarette and current ENDS use when compared with never cigarette and noncurrent ENDS use (AOR, 1.20; 95% CI, 0.83-1.72), and for odds of wheezing and current cigarette and current ENDS use when compared with current cigarette and noncurrent ENDS use (AOR, 1.02; 95% CI, 0.91-1.15).In this cohort study, exclusive ENDS use was not associated with an increase in the risk of self-reported wheezing. However, a small increase in risk between ENDS use and wheezing was reported by individuals who use cigarettes. This study adds to the literature about the potential health effects associated with ENDS use.
Accumulation of α-synuclein mediates podocyte injury in Fabry nephropathy
Authors: Fabian Braun, Ahmed Abed, Dominik Sellung, Manuel Rogg, Mathias Woidy, Oysten Eikrem, Nicola Wanner, Jessica Gambardella, Sandra D. Laufer, Fabian Haas, Milagros N. Wong, Bernhard Dumoulin, Paula Rischke, Anne Mühlig, Wiebke Sachs, Katharina von Cossel, Kristina Schulz, Nicole Muschol, Sören W. Gersting, Ania C. Muntau, Oliver Kretz, Oliver Hahn, Markus M. Rinschen, Michael Mauer, Tillmann Bork, Florian Grahammer, Wei Liang, Thorsten Eierhoff, Winfried Römer, Arne Hansen, Catherine Meyer-Schwesinger, Guido Iaccarino, Camilla Tøndel, Hans-Peter Marti, Behzad Najafian, Victor G. Puelles, Christoph Schell, Tobias B. Huber
Journal: Journal of Clinical Investigation (2023)

Current therapies for Fabry disease are based on reversing intracellular accumulation of globotriaosylceramide (Gb3) by enzyme replacement therapy (ERT) or chaperone-mediated stabilization of the defective enzyme, thereby alleviating lysosomal dysfunction. However, their effect in the reversal of end-organ damage, like kidney injury and chronic kidney disease, remains unclear. In this study, ultrastructural analysis of serial human kidney biopsies showed that long-term use of ERT reduced Gb3 accumulation in podocytes but did not reverse podocyte injury. Then, a CRISPR/Cas9-mediated α-galactosidase knockout podocyte cell line confirmed ERT-mediated reversal of Gb3 accumulation without resolution of lysosomal dysfunction. Transcriptome-based connectivity mapping and SILAC-based quantitative proteomics identified α-synuclein (SNCA) accumulation as a key event mediating podocyte injury. Genetic and pharmacological inhibition of SNCA improved lysosomal structure and function in Fabry podocytes, exceeding the benefits of ERT. Together, this work reconceptualizes Fabry-associated cell injury beyond Gb3 accumulation, and introduces SNCA modulation as a potential intervention, especially for patients with Fabry nephropathy.
Translational Neuroscience Approaches to Understanding Autism
Authors: Jeremy Veenstra-VanderWeele, Kally C. O’Reilly, Megan Y. Dennis, José M. Uribe-Salazar, David G. Amaral
Journal: American Journal of Psychiatry (2023)

While autism spectrum disorder affects nearly 2% of children in the United States, little is known with certainty concerning the etiologies and brain systems involved. This is due, in part, to the substantial heterogeneity in the presentation of the core symptoms of autism as well as the great number of co-occurring conditions that are common in autistic individuals. Understanding the neurobiology of autism is further hampered by the limited availability of postmortem brain tissue to determine the cellular and molecular alterations that take place in the autistic brain. Animal models therefore provide great translational value in helping to define the neural systems that constitute the social brain and mediate repetitive behaviors or interests. If they are based on genetic or environmental factors that contribute to autism, organisms from flies to nonhuman primates may serve as models of the neural structure or function of the autistic brain. Ultimately, successful models can also be employed to test the safety and effectiveness of potential therapeutics. This is an overview of the major animal species that are currently used as models of autism, including an appraisal of the advantages and limitations of each.
In BPPV, canalith repositioning maneuver increased symptom resolution vs. vestibular suppressants
Authors: KoKo Aung, Thwe Htay
Journal: Annals of Internal Medicine (2023)

Source Citation Sharif S, Khoujah D, Greer A, et al. Vestibular suppressants for benign paroxysmal positional vertigo: a systematic review and meta-analysis of randomized controlled trials. Acad Emerg Med. 2022. [Epub ahead of print.] 36268806
Community Health Worker Integration with and Effectiveness in Health Care and Public Health in the United States
Authors: Molly Knowles, Aidan P. Crowley, Aditi Vasan, Shreya Kangovi
Journal: Annual Review of Public Health (2023)

Community health workers (CHWs) have worked in a variety of settings in the United States for more than 70 years and are increasingly recognized as an essential health workforce. CHWs share life experience with the people they serve and have firsthand knowledge of the causes and impacts of health inequity. They provide a critical link between marginalized communities and health care and public health services. Several studies have demonstrated that CHWs can improve the management of chronic conditions, increase access to preventive care, improve patients’ experience of care, and reduce health care costs. CHWs can also advance health equity by addressing social needs and advocating for systems and policy change. This review provides a history of CHW integration with health care in the United States; describes evidence of the impact of CHW programs on population health, experience, costs of care, and health equity; and identifies considerations for CHW program expansion.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2023)

Breaking Insights| April 04 2023 Highlights from Recent Cancer Literature Author & Article Information Online ISSN: 1538-7445 Print ISSN: 0008-5472 ©2023 American Association for Cancer Research2023American Association for Cancer Research Cancer Res (2023) 83 (7): 975–976. https://doi.org/10.1158/0008-5472.CAN-83-7-BI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record April 4 2023 Citation Highlights from Recent Cancer Literature. Cancer Res 1 April 2023; 83 (7): 975–976. https://doi.org/10.1158/0008-5472.CAN-83-7-BI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Although EGFR inhibitors have high response rates in EGFR mutant non-small cell lung cancer (NSCLC), 30% of patients fail to respond. Wang and colleagues developed a histology-based digital-staining predictive model for EGFR inhibitors. Utilizing a standard hematoxylin and eosin slide, they demonstrated that tumor–tumor interactions predicted for better survival, while tumor–stroma interactions predicted for worse survival. Tumors in the “predicted benefitting group” had expression features associated with proliferation and activation of p53, while tumors in the “predicted non-benefitting group” had expression signatures associated with the HGF/MET, PI3K/AKT, and EMT pathways. Expert Commentary: The authors have developed a universally applicable predictive model for EGFR TKI efficacy, which could be widely adopted in clinical practice. Wang S, Rong R, Yang DM, Fujimoto J, Bishop JA, Yan S, et al. Features of tumor-microenvironment images predict targeted therapy survival benefit in patients with EGFR-mutant lung cancer. J Clin Invest 2023;133:e160330. doi: 10.1172/JCI160330. The tumor... You do not currently have access to this content.
Evolving Real-World Effectiveness of Monoclonal Antibodies for Treatment of COVID-19
Authors: Kevin E. Kip, Erin K. McCreary, Kevin Collins, Tami E. Minnier, Graham M. Snyder, William Garrard, Jeffrey C. McKibben, Donald M. Yealy, Christopher W. Seymour, David T. Huang, J. Ryan Bariola, Mark Schmidhofer, Richard J. Wadas, Derek C. Angus, Paula L. Kip, Oscar C. Marroquin
Journal: Annals of Internal Medicine (2023)

Background: Treatment guidelines and U.S. Food and Drug Administration emergency use authorizations (EUAs) of monoclonal antibodies (mAbs) for treatment of high-risk outpatients with mild to moderate COVID-19 changed frequently as different SARS-CoV-2 variants emerged. Objective: To evaluate whether early outpatient treatment with mAbs, overall and by mAb product, presumed SARS-CoV-2 variant, and immunocompromised status, is associated with reduced risk for hospitalization or death at 28 days. Design: Hypothetical pragmatic randomized trial from observational data comparing mAb-treated patients with a propensity score–matched, nontreated control group. Setting: Large U.S. health care system. Participants: High-risk outpatients eligible for mAb treatment under any EUA with a positive SARS-CoV-2 test result from 8 December 2020 to 31 August 2022. Intervention: Single-dose intravenous mAb treatment with bamlanivimab, bamlanivimab–etesevimab, sotrovimab, bebtelovimab, or intravenous or subcutaneous casirivimab–imdevimab administered within 2 days of a positive SARS-CoV-2 test result. Measurements: The primary outcome was hospitalization or death at 28 days among treated patients versus a nontreated control group (no treatment or treatment ≥3 days after SARS-CoV-2 test date). Results: The risk for hospitalization or death at 28 days was 4.6% in 2571 treated patients and 7.6% in 5135 nontreated control patients (risk ratio [RR], 0.61 [95% CI, 0.50 to 0.74]). In sensitivity analyses, the corresponding RRs for 1- and 3-day treatment grace periods were 0.59 and 0.49, respectively. In subgroup analyses, those receiving mAbs when the Alpha and Delta variants were presumed to be predominant had estimated RRs of 0.55 and 0.53, respectively, compared with 0.71 for the Omicron variant period. Relative risk estimates for individual mAb products all suggested lower risk for hospitalization or death. Among immunocompromised patients, the RR was 0.45 (CI, 0.28 to 0.71). Limitations: Observational study design, SARS-CoV-2 variant presumed by date rather than genotyping, no data on symptom severity, and partial data on vaccination status. Conclusion: Early mAb treatment among outpatients with COVID-19 is associated with lower risk for hospitalization or death for various mAb products and SARS-CoV-2 variants. Primary Funding Source: None.
Moving Spatially Resolved Multiplexed Protein Profiling toward Clinical Oncology
Authors: Maryam Pourmaleki, Nicholas D. Socci, Travis J. Hollmann, Ingo K. Mellinghoff
Journal: Cancer Discovery (2023)

Summary: The shift in cancer therapy from broadly cytotoxic agents toward “personalized” treatments that target specific alterations in each patient's tumor requires diagnostic pathology approaches that are quantitative and biospecimen-friendly. Novel multiplexed antibody-based imaging technologies can measure single-cell expression of over 60 proteins in intact tumor sections and hold promise for clinical oncology.
Collagen-Anchored Interleukin-2 and Interleukin-12 Safely Reprogram the Tumor Microenvironment in Canine Soft-Tissue Sarcomas
Authors: Jordan A. Stinson, Allison Sheen, Noor Momin, Jordan Hampel, Rebecca Bernstein, Rebecca Kamerer, Bahaa Fadl-Alla, Jonathan Samuelson, Elizabeth Fink, Timothy M. Fan, K. Dane Wittrup
Journal: Clinical Cancer Research (2023)

Cytokine therapies such as IL2 and IL12 suffer from impractically small therapeutic windows driven by their on-target, off-tumor activity, limiting their clinical potential despite potent antitumor effects. We previously engineered cytokines that bind and anchor to tumor collagen following intratumoral injection, and sought to test their safety and biomarker activity in spontaneous canine soft-tissue sarcomas (STS).Collagen-binding cytokines were canine-ized to minimize immunogenicity and were used in a rapid dose-escalation study in healthy beagles to identify a maximum tolerated dose. Ten client-owned pet dogs with STS were then enrolled into trial, receiving cytokines at different intervals prior to surgical tumor excision. Tumor tissue was analyzed through IHC and NanoString RNA profiling for dynamic changes within treated tumors. Archived, untreated STS samples were analyzed in parallel as controls.Intratumorally administered collagen-binding IL2 and IL12 were well tolerated by STS-bearing dogs, with only Grade 1/2 adverse events observed (mild fever, thrombocytopenia, neutropenia). IHC revealed enhanced T-cell infiltrates, corroborated by an enhancement in gene expression associated with cytotoxic immune function. We found concordant increases in expression of counter-regulatory genes that we hypothesize would contribute to a transient antitumor effect, and confirmed in mouse models that combination therapy to inhibit this counter-regulation can improve responses to cytokine therapy.These results support the safety and activity of intratumorally delivered, collagen-anchoring cytokines for inflammatory polarization of the canine STS tumor microenvironment. We are further evaluating the efficacy of this approach in additional canine cancers, including oral malignant melanoma.
Pembrolizumab and cabozantinib in recurrent metastatic head and neck squamous cell carcinoma: a phase 2 trial
Authors: Nabil F. Saba, Conor E. Steuer, Asari Ekpenyong, Ashley McCook-Veal, Kelly Magliocca, Mihir Patel, Nicole C. Schmitt, William Stokes, James E. Bates, Soumon Rudra, Jill Remick, Mark McDonald, Marin Abousaud, Aik Choon Tan, Muhammad Zaki Hidayatullah Fadlullah, Ritu Chaudhary, Jameel Muzaffar, Kedar Kirtane, Yuan Liu, Georgia Z. Chen, Dong M. Shin, Yong Teng, Christine H. Chung
Journal: Nature Medicine (2023)
TGF-β signaling promotes cervical cancer metastasis via CDR1as
Authors: Guanglei Zhong, Qian Zhao, Zhiliao Chen, Tingting Yao
Journal: Molecular Cancer (2023)

Abstract Background Due to the lack of effective treatment, metastasis is the main cause of cancer related deaths. TGF-β pathway has been reported related to cervical cancer metastasis. However, mechanism is still unclear. Methods After agonist of TGF-β treatment, RNA sequencing revealed the expression profiles of circRNA in cervical cancer. In situ hybridization was used to analysis relationship between CDR1as and prognosis. Real-time PCR, Western blot, RNA interference, Transwell assay, Wound healing assay, RNA pulldown assay and RIP assays were performed in vitro. And in vivo cervical cancer model (including foot pad model and subcutaneous tumor formation) was also performed. Results CDR1as was found upregulated obviously following TGF-β activation. In situ hybridization showed CDR1as was positively correlated with lymph node metastasis and shortened survival length. Simultaneously, overexpression of CDR1as promoted cervical cancer metastasis in vitro and in vivo. It was also found that CDR1as could facilitate the orchestration of IGF2BP1 on the mRNA of SLUG and stabilize it from degradation. Silencing IGF2BP1 hampers CDR1as related metastasis in cervical cancer. Additionally, effective CDR1as has been proven to activate TGF-β signaling factors known to promote EMT, including P-Smad2 and P-Smad3. Conclusions Our study proved TGF-β signaling may promote cervical cancer metastasis via CDR1as.
Childhood Cancer Treatment and Clonal Hematopoiesis
Authors: Grace Collord, Sam Behjati
Journal: Cancer Discovery (2023)

Summary: Hagiwara and colleagues investigated the effects of childhood cancer treatment on the clonal composition of blood. Their findings provide strong evidence that treatment promotes clonal outgrowths (clonal hematopoiesis) in childhood cancer survivors. See related article by Hagiwara et al., p. 844 (4).
High-throughput spatiotemporal monitoring of single-cell secretions via plasmonic microwell arrays
Authors: Saeid Ansaryan, Yen-Cheng Liu, Xiaokang Li, Augoustina Maria Economou, Christiane Sigrid Eberhardt, Camilla Jandus, Hatice Altug
Journal: Nature Biomedical Engineering (2023)

Methods for the analysis of cell secretions at the single-cell level only provide semiquantitative endpoint readouts. Here we describe a microwell array for the real-time spatiotemporal monitoring of extracellular secretions from hundreds of single cells in parallel. The microwell array incorporates a gold substrate with arrays of nanometric holes functionalized with receptors for a specific analyte, and is illuminated with light spectrally overlapping with the device's spectrum of extraordinary optical transmission. Spectral shifts in surface plasmon resonance resulting from analyte-receptor bindings around a secreting cell are recorded by a camera as variations in the intensity of the transmitted light while machine-learning-assisted cell tracking eliminates the influence of cell movements. We used the microwell array to characterize the antibody-secretion profiles of hybridoma cells and of a rare subset of antibody-secreting cells sorted from human donor peripheral blood mononuclear cells. High-throughput measurements of spatiotemporal secretory profiles at the single-cell level will aid the study of the physiological mechanisms governing protein secretion.